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Frankie Gustine was just 16 years old when he was scouted and signed by the Pittsburgh Pirates third base great, Pie Traynor, before the 1937 season. Frankie was destined to become the Pittsburgh club's infielder of the 1940s. Gustine spent three years in the minors, (1937-1939), working his way up, and hit an even .300 in 137 games, with 8 home runs, also playing third base at a .947 percentage for the class B Gadsden Pilots of the Southeastern League in 1939. He was called up to the Pirates late that year, appearing in 22 games and played well enough to stay on until 1949.

After first coming up in 1939, he was an everyday player in the Pittsburgh infield from 1940 through 1948, primarily at second base from 1940 to 1942 and in 1946, shortstop from from 1943 to 1945, and at third base in 1947 and 1948. He hit a career high .297 in 1947, playing all of his team's 156 games and leading all National League third basemen in putouts and assists. He was an All-Star at second base in 1946 and at third base in 1947 and 1948. Lifetime he hit .265 in a dozen seasons, also playing the infield at a .946 clip.

Gustine was the head coach at Point Park College from 1968 to 1974 and an administrator at the school. He was inducted into the school's Hall of Fame in 2000.

Gustine was befriended by both Pie Traynor and Honus Wagner during his career, and served as a pallbearer at the funerals of both Pirates Hall of Famers. Frankie was in Davenport, Iowa, for the first voyage of the President, a casino riverboat owned by John E. Connelly, his partner in ownership of the Sheraton Inn at Station Square in Pittsburgh, when he died from a heart attack on April 1, 1991 at age 71.